Submissions for variant NM_000059.4(BRCA2):c.7792G>T (p.Glu2598Ter)

dbSNP: rs1135401919

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)	RCV000661829	SCV000784152	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 2	2017-12-15	reviewed by expert panel	curation	Variant allele predicted to encode a truncated non-functional protein.
Ambry Genetics	RCV000573230	SCV000668692	pathogenic	Hereditary cancer-predisposing syndrome	2022-01-24	criteria provided, single submitter	clinical testing	The p.E2598* pathogenic mutation (also known as c.7792G>T), located in coding exon 15 of the BRCA2 gene, results from a G to T substitution at nucleotide position 7792. This changes the amino acid from a glutamic acid to a stop codon within coding exon 15. This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
Invitae	RCV000496865	SCV000759135	pathogenic	Hereditary breast ovarian cancer syndrome	2023-08-07	criteria provided, single submitter	clinical testing	This variant has not been reported in the literature in individuals affected with BRCA2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Glu2598*) in the BRCA2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BRCA2 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. ClinVar contains an entry for this variant (Variation ID: 431335).
GeneDx	RCV000657715	SCV000779464	pathogenic	not provided	2021-03-05	criteria provided, single submitter	clinical testing	Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Has not been previously published as pathogenic or benign to our knowledge; Not observed in large population cohorts (Lek 2016); Truncating variants in this gene are considered pathogenic by a well-established clinical consortium and/or database; Also known as 8020G>T; This variant is associated with the following publications: (PMID: 31076742)
Baylor Genetics	RCV003476192	SCV004211835	pathogenic	Familial cancer of breast	2023-10-20	criteria provided, single submitter	clinical testing
Mayo Clinic Laboratories, Mayo Clinic	RCV000657715	SCV004226632	pathogenic	not provided	2023-01-05	criteria provided, single submitter	clinical testing	PP5, PM2, PVS1
Research Molecular Genetics Laboratory, Women's College Hospital, University of Toronto	RCV000496865	SCV000587909	pathogenic	Hereditary breast ovarian cancer syndrome	2014-01-31	no assertion criteria provided	research